Differentiated cells in prolonged hypoxia produce highly infectious native‐like hepatitis C virus particles

Hepatology ◽  
2021 ◽  
Author(s):  
Jade Cochard ◽  
Anne Bull‐Maurer ◽  
Clovis Tauber ◽  
Julien Burlaud‐Gaillard ◽  
Frédéric Mazurier ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Particles ◽  
Differentiated Cells

Floating density of hepatitis C virus particles and response to interferon treatment

1998 ◽  
Vol 55 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Akito Sakai ◽  
Shuichi Kaneko ◽  
Eiki Matsushita ◽  
Kenichi Kobayashi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Treatment ◽  
Virus Particles

scholarly journals Building a mechanistic mathematical model of hepatitis C virus entry

2018 ◽  
Author(s):  
Mphatso Kalemera ◽  
Dilyana Mincheva ◽  
Joe Grove ◽  
Christopher J. R. Illingworth
Keyword(s):  
Mathematical Model ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Productive Infection ◽  
Virus Particles ◽  
Quantitative Studies ◽  
Receptor Dynamics ◽  
Viral Lifecycle ◽  
The Impact

AbstractThe mechanism by which hepatitis C virus (HCV) gains entry into cells is a complex one, involving a broad range of host proteins. Entry is a critical phase of the viral lifecycle, and a potential target for therapeutic or vaccine-mediated intervention. However, the mechanics of HCV entry remain poorly understood. Here we describe a novel computational model of viral entry, encompassing the relationship between HCV and the key host receptors CD81 and SR-B1. We conduct experiments to thoroughly quantify the influence of an increase or decrease in receptor availability upon the extent of viral entry. We use these data to build and parameterise a mathematical model, which we then validate by further experiments. Our results are consistent with sequential HCV-receptor interactions, whereby initial interaction between the HCV E2 glycoprotein and SR-B1 facilitates the accumulation CD81 receptors, leading to viral entry. However, we also demonstrate that a small minority of virus can achieve entry in the absence of SR-B1. Our model estimates the impact of the different obstacles that viruses must surmount to achieve entry; among virus particles attaching to the cell surface, 20-35% accumulate sufficient CD81 receptors, of these 4-8% then complete the subsequent steps to achieve productive infection. Furthermore, we make estimates of receptor stoichiometry; between 3 and 6 CD81 receptors are likely to be required to achieve viral entry. Our model provides a tool to investigate the entry characteristics of HCV variants and outlines a framework for future quantitative studies of the multi-receptor dynamics of HCV entry.

scholarly journals Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles

2009 ◽  
Vol 91 (2) ◽  
pp. 362-372 ◽  
Author(s):  
L. Corless ◽  
C. M. Crump ◽  
S. D. C. Griffin ◽  
M. Harris
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Infectious Hepatitis ◽  
Virus Particles

Low density Hepatitis C virus particles (lipoviral particles) associate with insulin resistance in genotype 1 infection

2010 ◽  
Vol 213 (1) ◽  
pp. e4 ◽  
Author(s):  
S.H. Bridge ◽  
D.A. Sheridan ◽  
D.J. Felmlee ◽  
G.L. Toms ◽  
R.D.G. Neely ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Low Density ◽  
Genotype 1 ◽  
Virus Particles

scholarly journals Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles

2006 ◽  
Vol 80 (22) ◽  
pp. 11074-11081 ◽  
Author(s):  
Pablo Gastaminza ◽  
Sharookh B. Kapadia ◽  
Francis V. Chisari
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Buoyant Density ◽  
Infection Model ◽  
Virus Particles ◽  
Viral Egress ◽  
Viral Particles ◽  
A Cell ◽  
Infected Cells

ABSTRACT The recent development of a cell culture infection model for hepatitis C virus (HCV) permits the production of infectious particles in vitro. In this report, we demonstrate that infectious particles are present both within the infected cells and in the supernatant. Kinetic analysis indicates that intracellular particles constitute precursors of the secreted infectious virus. Ultracentrifugation analyses indicate that intracellular infectious viral particles are similar in size (∼65 to 70 nm) but different in buoyant density (∼1.15 to 1.20 g/ml) from extracellular particles (∼1.03 to 1.16 g/ml). These results indicate that infectious HCV particles are assembled intracellularly and that their biochemical composition is altered during viral egress.

scholarly journals Biochemical and Morphological Properties of Hepatitis C Virus Particles and Determination of Their Lipidome

2010 ◽  
Vol 286 (4) ◽  
pp. 3018-3032 ◽  
Author(s):  
Andreas Merz ◽  
Gang Long ◽  
Marie-Sophie Hiet ◽  
Britta Brügger ◽  
Petr Chlanda ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Morphological Properties ◽  
Virus Particles

scholarly journals Hepatitis C Virus Strain-Dependent Usage of Apolipoprotein E Modulates Assembly Efficiency and Specific Infectivity of Secreted Virions

2017 ◽  
Vol 91 (18) ◽  
Author(s):  
Romy Weller ◽  
Kathrin Hueging ◽  
Richard J. P. Brown ◽  
Daniel Todt ◽  
Sebastian Joecks ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Apolipoprotein E ◽  
Virus Production ◽  
Host Factor ◽  
Cell Entry ◽  
Cell Type ◽  
Virus Particles ◽  
Strain Dependent ◽  
Apoe Expression

ABSTRACT Hepatitis C virus (HCV) is extraordinarily diverse and uses entry factors in a strain-specific manner. Virus particles associate with lipoproteins, and apolipoprotein E (ApoE) is critical for HCV assembly and infectivity. However, whether ApoE dependency is common to all HCV genotypes remains unknown. Therefore, we compared the roles of ApoE utilizing 10 virus strains from genotypes 1 through 7. ApoA and ApoC also support HCV assembly, so they may contribute to virus production in a strain-dependent fashion. Transcriptome sequencing (RNA-seq) revealed abundant coexpression of ApoE, ApoB, ApoA1, ApoA2, ApoC1, ApoC2, and ApoC3 in primary hepatocytes and in Huh-7.5 cells. Virus production was examined in Huh-7.5 cells with and without ApoE expression and in 293T cells where individual apolipoproteins (ApoE1, -E2, -E3, -A1, -A2, -C1, and -C3) were provided in trans. All strains were strictly ApoE dependent. However, ApoE involvement in virus production was strain and cell type specific, because some HCV strains poorly produced infectious virus in ApoE-expressing 293T cells and because ApoE knockout differentially affected virus production of HCV strains in Huh-7.5 cells. ApoE allelic isoforms (ApoE2, -E3, and -E4) complemented virus production of HCV strains to comparable degrees. All tested strains assembled infectious progeny with ApoE in preference to other exchangeable apolipoproteins (ApoA1, -A2, -C1, and -C3). The specific infectivity of HCV particles was similar for 293T- and Huh-7.5-derived particles for most strains; however, it differed by more than 100-fold in some viruses. Collectively, this study reveals strain-dependent and host cell-dependent use of ApoE during HCV assembly. These differences relate to the efficacy of virus production and also to the properties of released virus particles and therefore govern viral fitness at the level of assembly and cell entry. IMPORTANCE Chronic HCV infections are a major cause of liver disease. HCV is highly variable, and strain-specific determinants modulate the response to antiviral therapy, the natural course of infection, and cell entry factor usage. Here we explored whether host factor dependency of HCV in particle assembly is modulated by strain-dependent viral properties. We showed that all examined HCV strains, which represent all seven known genotypes, rely on ApoE expression for assembly of infectious progeny. However, the degree of ApoE dependence is modulated in a strain-specific and cell type-dependent manner. This indicates that HCV strains differ in their assembly properties and host factor usage during assembly of infectious progeny. Importantly, these differences relate not only to the efficiency of virus production and release but also to the infectiousness of virus particles. Thus, strain-dependent features of HCV modulate ApoE usage, with implications for virus fitness at the level of assembly and cell entry.

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